{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T11:51:53Z","timestamp":1791287513487,"version":"4.1.0"},"reference-count":25,"publisher":"Croatian Society for Medical Biochemistry and Laboratory Medicine","issue":"3","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Biochem. med. (Online)"],"published-print":{"date-parts":[[2026,10,15]]},"abstract":"<jats:p>Introduction: We aimed to compare total serum vitamin B12 measurements across four immunoassay platforms, establish method-specific reference intervals, evaluate the clinical impact of a uniform deficiency cut-off, and assess associations between total vitamin B12 and holotranscobalamin (holoTC).\nMaterials and methods: Residual serum samples from 220 apparently healthy adults undergoing routine health check-ups were analyzed. Total vitamin B12 was measured on Beckman, Abbott, Siemens, and Roche platforms. Beckman analyses used the updated Access Vitamin B12 II calibrator introduced in December 2024. Holotranscobalamin was measured on the Abbott system. Reference intervals were derived using non-parametric methods according to CLSI EP28-A3c guidelines. Method comparison was performed using Passing-Bablok regression and concordance correlation coefficients (CCC), and associations between total vitamin B12 and holoTC were assessed using Spearman correlation analysis.\nResults: Total vitamin B12 concentrations differed significantly across platforms, with moderate to good agreement (CCC: 0.81-0.91). Study-derived lower reference limits (LRLs) varied substantially between assays and differed from manufacturer-provided values, most prominently for the Beckman platform. Application of a fixed deficiency cut-off of 148 pmol\/L resulted in marked method-dependent differences in deficiency classification. Correlations between total vitamin B12 and holoTC were low to moderate across analytical platforms.\nConclusions: Serum vitamin B12 results vary across platforms, causing method-dependent LRLs and inconsistent classification with uniform cut-offs, underscoring the need for method-specific interpretation and improved harmonization. Low-to-moderate correlations reflect that holoTC and total vitamin B12 represent different components of vitamin B12 status and that total vitamin B12 assays differ by platform in reflecting the active fraction.<\/jats:p>","DOI":"10.11613\/bm.2026.030705","type":"journal-article","created":{"date-parts":[[2026,10,2]],"date-time":"2026-10-02T09:08:08Z","timestamp":1790932088000},"page":"534-542","source":"Crossref","is-referenced-by-count":0,"title":["Determination of method-specific reference intervals for vitamin B12 and its correlation with holotranscobalamin"],"prefix":"10.11613","volume":"36","author":[{"given":"Ozlem C.","family":"Madenci","sequence":"first","affiliation":[{"name":"Department of Clinical Biochemistry, Kartal Dr Lutfi Kirdar City Hospital, Istanbul, Turkey"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ebru","family":"Ertug","sequence":"additional","affiliation":[{"name":"Department of Clinical Biochemistry, Kartal Dr Lutfi Kirdar City Hospital, Istanbul, Turkey"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nazire","family":"Aladag","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, Kartal Dr Lutfi Kirdar City Hospital, Istanbul, Turkey"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ferruh K.","family":"Isman","sequence":"additional","affiliation":[{"name":"Department of Clinical Biochemistry, Medeniyet University, Istanbul, Turkey"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ibrahim","family":"Y\u0131lmaz","sequence":"additional","affiliation":[{"name":"Department of Clinical Biochemistry, Haseki Training and Research Hospital, Istanbul, Turkey"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"4885","published-online":{"date-parts":[[2026,10,15]]},"reference":[{"key":"key20261002090801_r1","doi-asserted-by":"crossref","DOI":"10.1136\/bmj-2022-071725","article-title":"Vitamin 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Biochem"},{"key":"key20261002090801_r9","doi-asserted-by":"crossref","first-page":"1102","DOI":"10.1093\/clinchem\/hvaf037","article-title":"Vitamin B12 Deficiency and New Recommendations by the National Institute for Health and Care Excellence: A Challenging Clinical and Laboratory Topic.","volume":"71","author":"Ferraro","year":"2025","journal-title":"Clin Chem"},{"key":"key20261002090801_r10","doi-asserted-by":"crossref","first-page":"2433","DOI":"10.1515\/cclm-2025-0939","article-title":"Assessing the harmonization of current total vitamin B12 measurement methods: relevance and implications.","volume":"63","author":"Cesana","year":"2025","journal-title":"Clin Chem Lab Med"},{"key":"key20261002090801_r11","doi-asserted-by":"crossref","first-page":"496","DOI":"10.1111\/bjh.12959","article-title":"Guidelines for the diagnosis and treatment of cobalamin and folate disorders.","volume":"166","author":"Devalia","year":"2014","journal-title":"Br J Haematol"},{"key":"key20261002090801_r12","doi-asserted-by":"crossref","first-page":"S238","DOI":"10.1177\/15648265080292S129","article-title":"Conclusions of a WHO Technical Consultation on folate and vitamin B12 deficiencies.","volume":"29","author":"de Benoist","year":"2008","journal-title":"Food Nutr Bull"},{"key":"key20261002090801_r13","unstructured":"Beckman Coulter. Access Vitamin B12 II assay: instructions for use. Brea (CA): Beckman Coulter; 2024. Available from: https:\/\/www.beckmancoulter.com. Accessed August 15th 2025."},{"key":"key20261002090801_r14"},{"key":"key20261002090801_r15"},{"key":"key20261002090801_r16"},{"key":"key20261002090801_r17","doi-asserted-by":"crossref","first-page":"299","DOI":"10.3390\/nu2030299","article-title":"Vitamin B12 and folate deficiency.","volume":"2","author":"O\u2019Leary","year":"2010","journal-title":"Nutrients"},{"key":"key20261002090801_r18"},{"key":"key20261002090801_r19"},{"key":"key20261002090801_r20","doi-asserted-by":"crossref","first-page":"158","DOI":"10.1093\/ajcn\/nqz045","article-title":"Age-specific reference ranges are needed to interpret serum methylmalonic acid concentrations in the US population.","volume":"110","author":"Mineva","year":"2019","journal-title":"Am J Clin Nutr"},{"key":"key20261002090801_r21","doi-asserted-by":"crossref","first-page":"1205","DOI":"10.1515\/cclm-2014-0843","article-title":"Comparison of four automated serum vitamin B12 assays.","volume":"53","author":"\u0130spir","year":"2015","journal-title":"Clin Chem Lab Med"},{"key":"key20261002090801_r22","doi-asserted-by":"crossref","first-page":"420","DOI":"10.1080\/10408363.2018.1482256","article-title":"Distinguishing reference intervals and clinical decision limits: a review by the IFCC committee on reference intervals and decision limits.","volume":"55","author":"Ozarda","year":"2018","journal-title":"Crit Rev Clin Lab Sci"},{"key":"key20261002090801_r23","doi-asserted-by":"crossref","first-page":"184","DOI":"10.1258\/acb.2011.011039","article-title":"Screening for metabolic vitamin B12 deficiency by holotranscobalamin in patients suspected of vitamin B12 deficiency: a multicentre study.","volume":"49","author":"Heil","year":"2012","journal-title":"Ann Clin Biochem"},{"key":"key20261002090801_r24","article-title":"Strategic use of Big Data: implementing reference intervals for serum folate and serum cobalamin.","volume":"35","author":"Madurga","year":"2025","journal-title":"Biochem Med (Zagreb)"},{"key":"key20261002090801_r25","doi-asserted-by":"crossref","first-page":"4035","DOI":"10.4103\/jfmpc.jfmpc_422_24","article-title":"The reference value of serum vitamin B12 among An-Najah National University students.","volume":"13","author":"Alnees","year":"2024","journal-title":"J Family Med Prim Care"}],"container-title":["Biochemia medica"],"original-title":[],"link":[{"URL":"https:\/\/www.biochemia-medica.com\/en\/journal\/36\/3\/10.11613\/BM.2026.030705\/fullArticle","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T11:03:03Z","timestamp":1791284583000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.biochemia-medica.com\/en\/journal\/36\/3\/10.11613\/BM.2026.030705"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,10,15]]},"references-count":25,"journal-issue":{"issue":"3","published-online":{"date-parts":[[2026,10,5]]},"published-print":{"date-parts":[[2026,10,15]]}},"URL":"https:\/\/doi.org\/10.11613\/bm.2026.030705","relation":{},"ISSN":["1846-7482","1330-0962"],"issn-type":[{"value":"1846-7482","type":"electronic"},{"value":"1330-0962","type":"print"}],"subject":[],"published":{"date-parts":[[2026,10,15]]}}}